(SS#I) Elekta Tumor Section Award (2023 Award Winner): Amine Chemical Exchange Saturation Transfer Echo Planar Imaging (CEST-EPI) Visualizes Infiltrating Glioblastoma Cells and Prognosticates Progression Free Survival in New and Recurrent Glioblastoma
Resident Physician University of California, Los Angeles Los Angeles, California, United States
Disclosure(s):
Kunal S. Patel, MD: No financial relationships to disclose
Introduction: Given the invasive nature of glioblastoma and pattern of recurrence, tumor cells exist beyond the contrast enhancing (CE) region of glioblastoma, but this non-enhancing (NE) tumor is difficult to visualize. Amine chemical exchange saturation transfer echo planar imaging (CEST-EPI) is a pH sensitive MRI sequence that can be applied to further visualize tumor extent in glioblastoma.
Methods: In 70 patients, amine CEST-EPI was obtained and CEST+ NE regions of interest (ROI) were quantitatively segmented. Median CEST contrast (asymmetry in magnetization transfer ratio or MTRasym) and volume of CEST positive NE regions were correlated with survival. Prospective image guided biopsies of these areas were obtained to correlate MTRasym to tumor and non-tumor cell burden using immunohistochemistry and single cell RNA sequencing.
Results: In both newly diagnosed and recurrent glioblastoma median MTRasym of CEST+ NE regions was associated with decreased progression free survival [p=0.007; p=0.0326]. Volume of CEST+ NE regions was associated with decreased progression free survival [p=0.020; p< 0.001]. MTRasym correlated with cell density and %Ki-67 positivity [p=0.009; p=0.004], confirmed with quantitation using single cell RNA sequencing.
Conclusion : Amine CEST-EPI visualizes infiltrating tumor cells. CEST+ NE ROIs correlate with survival and correspond to areas of tumor burden and active replication. Amine CEST-EPI can be used to increase extent of resection of glioblastoma and identify infiltrating glioblastoma cells for further study.